Paroxysmal nocturnal hemoglobinuria is characterized by blood cells which lack defense mechanism against attack by complement. In the current request, we plan to study the biochemical basis of this defect. We will study the interaction of the components of the terminal complex of complement with the membrane of the PNH III cell and normal cells which are altered to resemble this cell. In particular, we will investigate the interaction of the fluid-phase generated C5b-6(7) complex to determine the factors that facilitate its interaction with the PNH III cells. Further, we will investigate the interaction of the components of the assembled membrane attack complex with membrane proteins, seeking in particular proteins of the normal red cell membrane which interact with complement components but which are lacking on PNH III cells. Since all of the proteins which have been found to be missing on PNH cells (decay accelerating factor, acetylcholinesterase, alkaline phosphatase) are known to sensitive to phosphatidyl inositol specific phospholipase C, we will seek to determine the relationship of this to the abnomalities of PNH. We will examine other proteins which are thought to bear the same achoring mechanism to see if they are missing on PNH. We will use specific lipases to determine if the defects characteristic of PNH can be reproduced. We will use cultured cells to determine if the defect is acquired during maturation and to determine the reasons for the loss of these proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK031379-07
Application #
3483603
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1982-07-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705